The proliferation of rat estrogen (E)-sensitive pituitary and mammary tumor cells in an "in animal-in culture" system will be studied. The effect of estradiol-17 beta (E2) on specific protein synthesis and its relation with the proliferation of these E2 target cells will be characterized. These cells carry estrophilins and multiply faster in animals to which E2 is administered than in those in which E2 is lacking. These tumor cells are prevented from proliferating in rats during the perinatal period and in alpha-fetoprotein (AFP)-secreting hepatomabearing isogenic rats. AFP is likely to be the cell multiplication inhibitor in these circumstances according to experiments carried out with animals and in culture. Other estrophilin-carrying cells that behave autonomously when injected into rats supplemented with E2 do not recognize the inhibitory properties of AFP. Further characterization of the interaction of AFP and E2-sensitive cells will be done. On the basis of evidence that indicates that E2 affects cell multiplication of its target cells in an indirect and negative fashion, data are being gathered from experiments with rat and human (MCF7) cells. So far, results are compatible with the proposition for a significant role played by circulating and intracellular (shut-off mechanism) inhibitors of cell proliferation. Efforts to characterize and purify these inhibitors are currently under way.